Inhibition of acid secretion in gastric parietal cells by the Ca2+/calmodulin-dependent protein kinase II inhibitor KN-93

A novel Ca2+/calmodulin-dependent protein kinase II (CaM Kinase II) inhibitor, KN-93 potently inhibits gastric acid secretion from parietal cells. As previously reported (1), treatment of parietal cells with a selective inhibitor of CaM kinase II, KN-62 resulted in the inhibition of cholinergic-stimulated rabbit parietal cell secretion, whereas it failed to inhibit the histamine and forskolin response. In contrast effects of carbachol, histamine and forskolin were significantly inhibited by KN-93 with an IC50 of 0.15, 0.3 and 1 microM, respectively; these effects occurred without any changes in intracellular cyclic AMP and Ca2+ levels. In the present study we investigated the mechanism by which KN-93 acts upon the acid-secreting machinery of gastric parietal cells. Neither redistribution of the proton pump activity nor the morphological transformation were affected by KN-93. The drug only weakly inhibited the H+, K(+)-ATPase activity but strongly dissipated the proton gradient formed in the gastric membrane vesicles and reduced the volume of luminal space. Thus KN-93 acts at pH gradient formation whereas KN-62 acts only at CaM Kinase II.     

Microcavity distributed-feedback laser using dye-doped polymeric thin films

An organic microcavity laser, in which all the stacked polymer layers are doped with pyrromethene-567 dye, is presented. Singlemode laser oscillation at 568 nm was obtained that was located in the middle of the stopband. The lasing threshold was found to be 260 nJ/pulse, which corresponded to 300 muJ/cm² in the pulse energy density     

Texture and Formation Mechanism of Fibrous Calcium Hydroxyapatite Particles Prepared by Decomposition of Calcium–EDTA Chelates

The texture of fibrous calcium hydroxyapatite (Ca₁₀-(PO₄)₆(OH)₂, CaHAP) particles that were prepared by the decomposition of calcium–ethylenediaminetetraacetic acid (calcium–EDTA) chelates at 100°C under various pH conditions (pH values of 5–10) was investigated by various means. Well-crystallized fibrous CaHAPs were produced at pH .6. The stoichiometry of the CaHAPs with a chemical formula of Ca_{10− x} (HPO₄) _x (PO₄)_{6− x} (OH)_{2− x} (H₂O) _x was improved by increasing the decomposition pH. All the CaHAPs had unit-cell dimensions of a = 0.9436 ± 0.0003 nm and c = 0.6881 ± 0.0006 nm, exhibiting an enlarged a value. The finding of mesoporosity of CaHAPs by nitrogen gas (N₂) adsorption measurement indicated that the CaHAPs were produced by an agglomeration of primary particles. Furthermore, the nonstoichiometric CaHAPs that formed at pH 6 developed ultramicropores, which were accessible to water (H₂O) molecules but not to N₂ molecules, by the elimination of H₂O molecules that were adsorbed in interstices of primary particles in less-orderly crystallized CaHAPs and/or by dehydration of HPO₄²⁻ groups. These findings by gas adsorption techniques could give evidence for the agglomeration mechanism to attain a polycrystalline CaHAP, although they exhibited good crystallinity with large size.     

The impact of RFID technology on warehouse process innovation: A pilot project in the TPL industry

Using the value chain model which provides a process view, this longitudinal case study and simulation modeling analysis of a Canadian third-party logistics (TPL) supply chain provides some empirical support for the enabling role of RFID technology in effecting warehouse process innovation and optimization for the focal TPL firm. However, the findings of our study also reveal the RFID technology implementation costs as the key inhibitor of RFID widespread adoption and usage among suppliers. This, in turn, precluded the focal TPL firm from implementing the best optimum RFID solution to create better business value from the RFID project.     

Combination of biomolecular interaction analysis and mass spectrometric amino acid sequencing

We describe an approach for the combination of biomolecular interaction analysis (BIA) and electrospray tandem mass spectrometry (ESI/MS/MS) to obtain sequence information on the affinity-bound proteins on the sensor chip of BIA. The procedure is illustrated with stable and unstable interactions of recombinant proteins, i.e., histidine-tagged protein-Ni2+/NTA and 1,4,5-inositol trisphosphate receptor-ligand interactions. The E. coli lysates expressing the recombinant proteins were passed through the sensor chips, and biomolecular interactions were monitored in real time. The molecules detected on the sensor chip were digested by delivering proteolytic enzyme to the sensing flow cells. The resulting on-chip digested peptide mixture at the mid- to low-femtomole level was recovered on a microcapillary reversed-phase precolumn by an on-line system and analyzed using HPLC-MS/MS. In both cases, unambiguous sequence information on the recombinant proteins isolated on the sensor chip was obtained from only a single run of analysis. The combined BIA-MS/MS may prove to be a general and versatile system to discover novel biomolecular interactions and to analyze protein complexes.     

Relationship between Expression of Onco-Related miRNAs and the Endoscopic Appearance of Colorectal Tumors

Accumulating data indicates that certain microRNAs (miRNAs or miRs) are differently expressed in samples of tumors and paired non-tumorous samples taken from the same patients with colorectal tumors. We examined the expression of onco-related miRNAs in 131 sporadic exophytic adenomas or early cancers and in 52 sporadic flat elevated adenomas or early cancers to clarify the relationship between the expression of the miRNAs and the endoscopic morphological appearance of the colorectal tumors. The expression levels of miR-143, -145, and -34a were significantly reduced in most of the exophytic tumors compared with those in the flat elevated ones. In type 2 cancers, the miRNA expression profile was very similar to that of the exophytic tumors. The expression levels of miR-7 and -21 were significantly up-regulated in some flat elevated adenomas compared with those in exophytic adenomas. In contrast, in most of the miR-143 and -145 down-regulated cases of the adenoma-carcinoma sequence and in some of the de novo types of carcinoma, the up-regulation of oncogenic miR-7 and/or -21 contributed to the triggering mechanism leading to the carcinogenetic process. These findings indicated that the expression of onco-related miRNA was associated with the morphological appearance of colorectal tumors.     

Alterations in the enzyme activity and protein contents of protein disulfide isomerase in rat tissues during fasting and refeeding

Elevated level of cellular lipid peroxidation can increase the incidence of vascular disease. The mechanism by which ketosis causes accelerated cellular damage and vascular disease in diabetes is not known. This study was undertaken to test the hypothesis that elevated levels of ketone bodies increase lipid peroxidation in endothelial cells. Human umbilical venous endothelial cells (HUVEC) were cultured for 24 h at 37 degrees C with ketone bodies (acetoacetate, beta-hydroxybutyrate). Acetoacetate, but not beta-hydroxybutyrate, caused an increase in lipid peroxidation and growth inhibition in cultured HUVEC. To determine whether ketone bodies generate oxygen radicals, studies using cell-free buffered solution were performed. They showed a significant superoxide dismutase (SOD) inhibitable reduction of cytochrome C by acetoacetate, but not by beta-hydroxybutyrate, suggesting the generation of superoxide anion radicals by acetoacetate. Additional studies show that Fe2+ potentiates oxygen radical generation by acetoacetate. Thus, elevated levels of ketone body acetoacetate can generate oxygen radicals and cause lipid peroxidation in endothelial cells, providing a possible mechanism for the increased incidence of vascular disease in diabetes.     

Photoexcited states in directly synthesized trans-polyacetylene films studied by photocurrent measurement

A trans-polyacetylene film was directly synthesized to reduce defects introduced during usual thermal isomerization treatment. A photocurrent excitation spectrum of this film showed very low efficiency around a reflection peak which was accompanied with phonon side bands. This strongly indicates that the lowest optically allowed state of trans-polyacetylene is a 1¹B^u exciton state like other conjugated polymers, such as polydiacetylenes. Misinterpretations of the experimental results under the SSH model, because of the use of a film of low quality, are pointed out and reinterpretations are made according to the present conclusion.     

Effects of seasonings on physical properties and MRI T2 map of cooked spaghetti

The effect of seasonings on the texture of cooked spaghetti was examined by sensory and shearing tests. Spaghetti tossed with sucrose, trehalose, salt, and monosodium glutamate and their mixture retarded deterioration of the firmness of spaghetti strands. To investigate the penetration of water and seasonings, maps of spin–spin relaxation time and their profiles from the center to the surface of a spaghetti strand were acquired by magnetic resonance imaging. The homogenization of moisture distribution in cooked spaghetti during holding was delayed temporarily by salt owing to a back current caused by the gradient of salt content on the surface immediately after tossing. Monosodium glutamate rapidly penetrated into spaghetti strands and caused water T₂ decrease possibly owing to the decreased mobility of water molecules in starch gel, whereas the sweeteners hardly altered the T₂ maps. Salt and monosodium glutamate are considered to retard more effectively the deterioration of firmness of spaghetti.